feeding was associated with a reduction in risk (OR,?0.56; 95% CI, 0.47-0.66 for less then 10 years) that persisted for decades (OR,?0.83; 95% CI, 0.77-0.90 for ?30 years; P for trend?=?.02). Conclusions and Relevance Breastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.SIRT6 deacetylase activity improves stress resistance via gene silencing and genome maintenance. Here, we reveal a deacetylase-independent function of SIRT6, which promotes anti-apoptotic gene expression via the transcription factor GATA4. SIRT6 recruits TIP60 acetyltransferase to acetylate GATA4 at K328/330, thus enhancing its chromatin binding capacity. In turn, GATA4 inhibits the deacetylase activity of SIRT6, thus ensuring the local chromatin accessibility via TIP60-promoted H3K9 acetylation. Significantly, the treatment of doxorubicin (DOX), an anti-cancer chemotherapeutic, impairs the SIRT6-TIP60-GATA4 trimeric complex, blocking GATA4 acetylation and causing cardiomyocyte apoptosis. While GATA4 hyperacetylation-mimic retains the protective effect against DOX, the hypoacetylation-mimic loses such ability. Thus, the data reveal a novel SIRT6-TIP60-GATA4 axis, which promotes the anti-apoptotic pathway to prevent DOX toxicity. Targeting the trimeric complex constitutes a new strategy to improve the safety of DOX chemotherapy in clinical application. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Bacterial communities play crucial roles in the biogeochemical cycle of the surface sediments of freshwater lakes, but previous studies on bacterial community changes in this habitat have mostly been based on the total bacterial community (DNA level), while an exploration of the active microbiota at the RNA level has been lacking. Herein, we analyzed the bacterial communities in the surface sediments of Lake Taihu at the DNA and RNA levels. Using MiSeq sequencing and real-time quantification, we found that the sequencing and quantitative results obtained at the RNA level compared with the DNA level were more accurate in responding to the spatiotemporal dynamic changes of the bacterial community. Although both sequencing methods indicated that Proteobacteria, Chloroflexi, Acidobacteria, Nitrospirae, Bacteroidetes, and Actinobacteria were the dominant phyla, the co-occurrence network at the RNA level could better reflect the close relationship between microorganisms in the surface sediment. Additionally, further analysis showed that Prochlorococcus and Microcystis were the most relevant and dominant genera of Cyanobacteria in the total and active bacterial communities, respectively; our results also demonstrated that the analysis of Cyanobacteria-related groups at the RNA level was more 'reasonable'. © FEMS 2020.Changes in gene copy number contribute to genomic instability, the onset and progression of cancer, developmental abnormalities and adaptive potential. The origins of gene amplifications have remained elusive; however, DNA rereplication has been implicated as a source of gene amplifications. The inability to determine which sequences are rereplicated and under what conditions have made it difficult to determine the validity of the proposed models. Here we present Rerep-Seq, a technique that selectively enriches for rereplicated DNA in preparation for analysis by DNA sequencing that can be applied to any species. We validated Rerep-Seq by simulating DNA rereplication in yeast and human cells. Using Rerep-Seq, we demonstrate that rereplication induced in Saccharomyces cerevisiae by deregulated origin licensing is non-random and defined by broad domains that span multiple replication origins and topological boundaries. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.Domestic wastewater is a recognized source of antibiotic resistant bacteria and antibiotic resistance genes (ARB&amp;ARGs), whose risk of transmission to humans cannot be ignored. The fitness of wastewater ARB in the complex fecal microbiota of a healthy human was investigated in feces-based microcosm assays (FMAs). FMAs were inoculated with two wastewater isolates, Escherichia coli strain A2FCC14 (MLST ST131) and Enterococcus faecium strain H1EV10 (MLST ST78), harboring the ARGs blaTEM, blaCTX, blaOXA-A and vanA, respectively. The FMAs, incubated in the presence or absence of oxygen or in the presence or absence of the antibiotics cefotaxime or vancomycin, were monitored based on cultivation, ARGs quantification and bacterial community analysis. The fecal bacterial community was dominated by members of the phyla Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Verrucomicrobia. The ARGs harbored by the wastewater isolates could be quantified after one week, in FMAs incubated under both aerobic and anaerobic conditions. https://www.selleckchem.com/products/mdivi-1.html These observations were not significantly different in FMAs incubated anaerobically, supplemented with sub-inhibitory concentrations of cefotaxime or vancomycin. The observation that ARGs of wastewater ARB persisted in presence of the human fecal microbiota for at least one week supports the hypothesis of a potential transmission to humans, a topic that deserves further investigation. © FEMS 2020.Importance Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants In this prospective, randomized (11 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior.